Compartmentalizing risk with sarcopenic obesity.

Sarcopenic obesity, the combination of decreased muscle mass combined with increased overall adipose content, is specifically associated with an increase in visceral adipose tissue.1 The distinction between visceral and subcutaneous adipose tissue is important as the former is more strongly associated with proinflammatory states including insulin resistance, ischemic heart disease, infection, and predisposition to some malignancies.2,3 In addition, higher levels of visceral fat have been found to be directly related to increasing stages of fibrosis in those with NAFLD.4 Sarcopenic obesity is known to be associated with an overall increased risk of mortality in cirrhosis patients,5 but the absence of a standardized definition has limited its utility for clinical research and risk stratification. The obesity component of sarcopenic obesity has been variously defined using body mass index, a predetermined visceral adipose tissue area, and visceral-to-subcutaneous adipose tissue ratio (VSR).5–7 Visceral location of increased adipose tissue appears to be a better marker for risk than total body adiposity.2,4 In this present issue of Liver Transplantation, Ha et al.8 examine the role of CT-quantified skeletal muscle index and VSR in defining sarcopenic visceral obesity (SVO) and in evaluating mortality in ambulatory adult patients with cirrhosis listed for liver transplantation. This single-center study drew patients from the Functional Assessment in Liver Transplantation (FrAILT) cohort. There were 326 adults with a median model for end-stage liver disease sodium of 13 who were followed for 12 months. The primary outcome was waitlist mortality, which included either death on the waiting list or being taken off the waiting list for the reason of being too ill for a transplant. Set cut-offs were determined for both skeletal muscle index and VSR separately for each gender. Forty-four percent of patients had sarcopenia only, 29% had visceral obesity only, and 13% met the criteria for both conditions. As expected, those with SVO had the highest waitlist mortality rate in comparison to sarcopenia only and visceral obesity only (40% vs. 21% vs. 12%, respectively). Univariable analysis continued to demonstrate a statistically significant increase in waitlist mortality when adjusted for variables such as liver frailty index, model for end-stage liver disease sodium, ascites, age, sex, diabetes, and different body compositions. The authors then compared VSR to previously established visceral obesity criteria including visceral adipose tissue area (≥100 cm2) and overall body mass index (≥25 kg/m2) and found that the data were no longer significant for waitlist mortality if using just the visceral adipose tissue area or body mass index. This is important as determining the VSR may allow for a more accurate predictive method of stratifying patients who have been diagnosed with sarcopenia and/or visceral obesity. Given the significant increase in waitlist mortality, how do we best address the role of SVO in our patients? Sarcopenic visceral obesity will now be incorporated as an additional risk factor when considering a candidacy for liver transplantation but, like sarcopenia and frailty, should not be used as a sole criterion to deny candidacy. Perhaps visceral obesity is a modifiable risk factor—in the general population, liraglutide, a GLP-1 receptor agonist, has demonstrated redistribution of body fat with an overall decrease in visceral fat and associated improvement in insulin resistance.9 There have also been promising results in cirrhosis patients—while not specifically looking at visceral adiposity, liraglutide has been found to improve NASH and also decrease the risk of progression of fibrosis.10 Although only a minority of the patients (13%) from the FrAILT cohort met the criteria for both sarcopenia and visceral obesity, the changing demographic of liver transplant candidates and the ongoing obesity epidemic means that the prevalence of SVO is likely increasing. In the cohort above, the most common etiology of cirrhosis was chronic hepatitis C (48%), whereas NASH only comprised 14%; these numbers do not accurately reflect current national data. NASH is now one of the leading indications for liver transplantation,11 and patients with NASH have a significantly increased risk of sarcopenic obesity.12 As the incidence of NASH-related cirrhosis continues to rise, and with it a rise in SVO, so increases the importance of learning to mitigate the risks of sarcopenia and obesity in liver transplantation. The authors are to be congratulated for their role in continuing to define how differences in body composition affect outcomes in liver transplantation. Studies are already demonstrating the ability to target visceral obesity in the general population, and we await more information on how these interventions specifically affect those with liver disease and cirrhosis. The ability to mitigate risk factors while awaiting liver transplantation will have significant implications for transplant programs and patients.